2-Trifluoromethyl cinchoninic acid, and substituted 2-trifluoromethyl cinchoninic acids, are known plant growth regulating materials. Such compounds can be prepared, as disclosed by B. M. Pinder and A. Burger (J. Med. Chem, 11, pp 267-269 (1968)), by condensation of aniline, or a substituted aniline, with ethyl 4,4,4-trifluoroacetoacetate in the presence of polyphosphoric acid to produce a 2-trifluoromethyl-4-hydroxyquinoline from which the desired 2-trifluoromethyl cinchoninic acid can be obtained by two alternative procedures. In the first of such procedures, the 2-trifluoromethyl-4-hydroxyquinoline is brominated with phosphorus oxybromide to produce the corresponding 2-trifluoromethyl-4-bromoquinoline which is then reacted with n-butyllithium to produce a lithioquinoline which can in turn be treated with dry carbon dioxide to produce the desired 2-trifluoromethyl cinchoninic acid. In the second of such procedures, the 2-trifluoromethyl-4-hydroxyquinoline is chlorinated with phosphorus oxychloride and the resulting 2-trifluoromethyl-4-chloroquinoline is reacted with cuprous cyanide in N-methylpyrrolidone to convert it to the corresponding nitrile which is then hydrolyzed to the desired 2-trifluoromethyl cinchoninic acid. However, not only are both these procedures complex and involved, but they produce yields of only about 35% and involve the use of corrosive materials such as phosphorus oxybromide and phosphorus oxychloride as well as air- and water-sensitive materials such a butyllithium and copper cyanide.
2-Methylcinchoninic acid has been prepared, as disclosed in Bull. Soc. Chem., France, 1956, 1294, by the reaction of isatin and acetone in 30 percent aqueous potassium hydroxide solution. However, it has been found that when isatin is reacted with 1,1,1-trifluoroacetone in an attempt to produce 2-trifluoromethyl cinchoninic acid in an analogous manner, the desired product cannot be obtained.
Although 2-trifluoromethyl cinchoninic acid can be obtained by hydrolyzing isatin in aqueous potassium hydroxide solution to form potassium 2-aminophenylglyoxylate and then reacting the latter product with 1,1,1-trifluoroacetone after adjusting the pH of the solution to 7 or below by means of a strong acid, the yields obtained by such process have been found not to exceed 40%.